Submissions for variant NM_000179.3(MSH6):c.1714C>T (p.Gln572Ter)

dbSNP: rs1064795256

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000487144	SCV000570885	pathogenic	not provided	2016-07-06	criteria provided, single submitter	clinical testing	This variant is denoted MSH6 c.1714C>T at the cDNA level and p.Gln572Ter (Q572X) at the protein level. The substitution creates a nonsense variant, which changes a Glutamine to a premature stop codon (CAG>TAG), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. Although this variant has not, to our knowledge, been reported in the literature, it is considered pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001036388	SCV001199749	pathogenic	Hereditary nonpolyposis colorectal neoplasms	2023-09-10	criteria provided, single submitter	clinical testing	ClinVar contains an entry for this variant (Variation ID: 421621). For these reasons, this variant has been classified as Pathogenic. This premature translational stop signal has been observed in individual(s) with clinical features of MSH6-related conditions (PMID: 10612827). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln572*) in the MSH6 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MSH6 are known to be pathogenic (PMID: 18269114, 24362816).
Ambry Genetics	RCV002402404	SCV002712953	pathogenic	Hereditary cancer-predisposing syndrome	2022-07-25	criteria provided, single submitter	clinical testing	The p.Q572* pathogenic mutation (also known as c.1714C>T), located in coding exon 4 of the MSH6 gene, results from a C to T substitution at nucleotide position 1714. This changes the amino acid from a glutamine to a stop codon within coding exon 4. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Myriad Genetics, Inc.	RCV003449215	SCV004185697	pathogenic	Lynch syndrome 5	2023-08-15	criteria provided, single submitter	clinical testing	This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV000487144	SCV001552670	uncertain significance	not provided		no assertion criteria provided	clinical testing
Medical Genetics Laboratory, Umraniye Training and Research Hospital, University of Health Sciences	RCV001643202	SCV001852757	pathogenic	Endometrial carcinoma	2021-09-12	no assertion criteria provided	clinical testing